Blood Pressure and Arsenic Exposure From Drinking Water
Blood Pressure and Arsenic Exposure From Drinking Water
The final study population included 10,853 participants, with median follow-up time of 6.7 years, ranging from 0.86 to 8.26 years. The median concentration was 62 μg/L for water arsenic and 88 μg/L for urinary arsenic, ranging from 0.1 to 864 μg/L and 1 to 2,273 μg/L, respectively. Of the study population, 9,070 had all four SBP measurements and 9,062 had all four DBP measurements; 1,150 had three SBP measurements and 1,159 had three DBP measurements; and 633 had two SBP measurements and 632 had two DBP measurements. There were 10,853 subjects with available water arsenic concentrations and 10,549 subjects with available baseline urinary creatinine-adjusted arsenic concentrations for analysis.
Individuals with lower baseline arsenic exposure were slightly more likely to have higher educational attainment or higher baseline BMI ( Table 1 ). There was no significant difference in SBP or DBP by water arsenic tertile groups at baseline, first follow-up, or second follow-up. However, there were global differences in SBP and DBP measured at the third visit in relation to baseline water arsenic levels. Baseline water arsenic levels were positively associated with urinary creatinine-adjusted arsenic levels at baseline, first follow-up, second follow-up, and third follow-up.
The rate of annual SBP increase tended to be greater with increasing baseline age ( Table 2 ). Age was inversely associated with the rate of longitudinal DBP increase. There was a monotonic decrease with increasing age, comparing older age groups (30–40, > 40 years of age) with younger age group (≤ 30 years of age), and the difference between the rate of DBP decrease among those > 40 years at baseline was close to being significantly lower than the rate among those ≤ 30 years at baseline. The data are consistent with previous literature that documented a decreasing DBP with increasing age (Wright et al. 2011). The annual increase in SBP was greater in women compared with men, in those with higher educational attainment than subjects with a lower educational attainment, and in those with a baseline BMI > 20.45 kg/m compared with 18.09–20.45 kg/m.
Table 3 and Table 4 show the associations of arsenic exposure categorized into quartiles and annual change in SBP or DBP. For SBP, we observed a positive association without a dose–response relationship throughout three models; individuals in the higher three quartiles of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in SBP compared with those in the reference group (β = 0.43–0.54 mmHg/year and β = 0.39–0.44 mmHg/year for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models ( Table 3 ). Likewise, for DBP, a positive relationship was also observed; individuals in the higher three quartiles of baseline arsenic exposure had a greater annual increase in DBP (β = 0.39–0.41 mmHg/year, and β = 0.37–0.45 mmHg/year for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models compared with those in the lowest quartile ( Table 4 ). For DBP there was a monotonic increase in the rate with increasing urinary creatinine-adjusted arsenic ( Table 4 ). Analyses using different categories of arsenic exposure (tertiles or quintiles) showed similar results (see Supplemental Material, Tables S2 and S3 http://ehp.niehs.nih.gov/wp-content/uploads/123/8/ehp.1409004.s001.acco.pdf). Sensitivity analyses were conducted by excluding all subjects who were under treatment for hypertension at baseline or follow-up (n = 545), without change in the overall results (data not shown). In an analysis of associations with changes in creatinine-adjusted urinary arsenic over time, with the least amount of change between visits (creatinine-adjusted urinary arsenic at later visit minus creatinine-adjusted urinary arsenic at earlier visit) as the reference group (ranging from a decrease of 9 to an increase of 39 μg/g creatinine), the greatest increase (> 39 μg/g creatinine) had a positive but nonsignificant association with the mean annual increase in SBP [β = 0.40; 95% confidence interval (CI): –0.04, 0.83] and DBP (β = 0.28; 95% CI: –0.03, 0.59), whereas there was no association with a decrease of > 9 μg/g creatinine over follow-up (data not shown). Because mean SBP and DBP both were highest at the second follow-up visit (suggesting a possible systematic error in measurement), we repeated analyses excluding follow-up 2 data but found similar results to analyses including data from all visits (data not shown).
Last, we assessed the association between baseline arsenic exposure and the absolute levels of BP at the third follow-up (see Supplemental Material, Figure S1 http://ehp.niehs.nih.gov/wp-content/uploads/123/8/ehp.1409004.s001.acco.pdf). In fully adjusted models, individuals with the highest level of baseline water arsenic had 3.95 mmHg (95% CI: 3.15, 4.76) greater SBP or 2.65 mmHg (95% CI: 2.21, 3.31) greater DBP compared with those in the reference group. Similarly, for urinary creatinine-adjusted arsenic, individuals with higher concentrations had a 3.47 mmHg (95% CI: 2.61, 4.33) increase in SBP or a 2.62 mmHg (95% CI: 1.95, 3.03) increase in DBP compared with those in the lowest quartile. However, associations were similar across quartiles 2, 3, and 4, without evidence of a monotonic trend (see Supplemental Material, Figure S1 http://ehp.niehs.nih.gov/wp-content/uploads/123/8/ehp.1409004.s001.acco.pdf).
Results
The final study population included 10,853 participants, with median follow-up time of 6.7 years, ranging from 0.86 to 8.26 years. The median concentration was 62 μg/L for water arsenic and 88 μg/L for urinary arsenic, ranging from 0.1 to 864 μg/L and 1 to 2,273 μg/L, respectively. Of the study population, 9,070 had all four SBP measurements and 9,062 had all four DBP measurements; 1,150 had three SBP measurements and 1,159 had three DBP measurements; and 633 had two SBP measurements and 632 had two DBP measurements. There were 10,853 subjects with available water arsenic concentrations and 10,549 subjects with available baseline urinary creatinine-adjusted arsenic concentrations for analysis.
Individuals with lower baseline arsenic exposure were slightly more likely to have higher educational attainment or higher baseline BMI ( Table 1 ). There was no significant difference in SBP or DBP by water arsenic tertile groups at baseline, first follow-up, or second follow-up. However, there were global differences in SBP and DBP measured at the third visit in relation to baseline water arsenic levels. Baseline water arsenic levels were positively associated with urinary creatinine-adjusted arsenic levels at baseline, first follow-up, second follow-up, and third follow-up.
The rate of annual SBP increase tended to be greater with increasing baseline age ( Table 2 ). Age was inversely associated with the rate of longitudinal DBP increase. There was a monotonic decrease with increasing age, comparing older age groups (30–40, > 40 years of age) with younger age group (≤ 30 years of age), and the difference between the rate of DBP decrease among those > 40 years at baseline was close to being significantly lower than the rate among those ≤ 30 years at baseline. The data are consistent with previous literature that documented a decreasing DBP with increasing age (Wright et al. 2011). The annual increase in SBP was greater in women compared with men, in those with higher educational attainment than subjects with a lower educational attainment, and in those with a baseline BMI > 20.45 kg/m compared with 18.09–20.45 kg/m.
Table 3 and Table 4 show the associations of arsenic exposure categorized into quartiles and annual change in SBP or DBP. For SBP, we observed a positive association without a dose–response relationship throughout three models; individuals in the higher three quartiles of baseline water arsenic or urinary creatinine-adjusted arsenic had a greater annual increase in SBP compared with those in the reference group (β = 0.43–0.54 mmHg/year and β = 0.39–0.44 mmHg/year for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models ( Table 3 ). Likewise, for DBP, a positive relationship was also observed; individuals in the higher three quartiles of baseline arsenic exposure had a greater annual increase in DBP (β = 0.39–0.41 mmHg/year, and β = 0.37–0.45 mmHg/year for water arsenic and urinary creatinine-adjusted arsenic, respectively) in fully adjusted models compared with those in the lowest quartile ( Table 4 ). For DBP there was a monotonic increase in the rate with increasing urinary creatinine-adjusted arsenic ( Table 4 ). Analyses using different categories of arsenic exposure (tertiles or quintiles) showed similar results (see Supplemental Material, Tables S2 and S3 http://ehp.niehs.nih.gov/wp-content/uploads/123/8/ehp.1409004.s001.acco.pdf). Sensitivity analyses were conducted by excluding all subjects who were under treatment for hypertension at baseline or follow-up (n = 545), without change in the overall results (data not shown). In an analysis of associations with changes in creatinine-adjusted urinary arsenic over time, with the least amount of change between visits (creatinine-adjusted urinary arsenic at later visit minus creatinine-adjusted urinary arsenic at earlier visit) as the reference group (ranging from a decrease of 9 to an increase of 39 μg/g creatinine), the greatest increase (> 39 μg/g creatinine) had a positive but nonsignificant association with the mean annual increase in SBP [β = 0.40; 95% confidence interval (CI): –0.04, 0.83] and DBP (β = 0.28; 95% CI: –0.03, 0.59), whereas there was no association with a decrease of > 9 μg/g creatinine over follow-up (data not shown). Because mean SBP and DBP both were highest at the second follow-up visit (suggesting a possible systematic error in measurement), we repeated analyses excluding follow-up 2 data but found similar results to analyses including data from all visits (data not shown).
Last, we assessed the association between baseline arsenic exposure and the absolute levels of BP at the third follow-up (see Supplemental Material, Figure S1 http://ehp.niehs.nih.gov/wp-content/uploads/123/8/ehp.1409004.s001.acco.pdf). In fully adjusted models, individuals with the highest level of baseline water arsenic had 3.95 mmHg (95% CI: 3.15, 4.76) greater SBP or 2.65 mmHg (95% CI: 2.21, 3.31) greater DBP compared with those in the reference group. Similarly, for urinary creatinine-adjusted arsenic, individuals with higher concentrations had a 3.47 mmHg (95% CI: 2.61, 4.33) increase in SBP or a 2.62 mmHg (95% CI: 1.95, 3.03) increase in DBP compared with those in the lowest quartile. However, associations were similar across quartiles 2, 3, and 4, without evidence of a monotonic trend (see Supplemental Material, Figure S1 http://ehp.niehs.nih.gov/wp-content/uploads/123/8/ehp.1409004.s001.acco.pdf).
